Metabolic syndrome (MetS), a condition that consists of five interconnected cardiometabolic risk factors, (ATP III, 2002; Grundy et al., 2005) increases the potential of developing atherosclerotic cardiovascular disease (ASCVD), Type 2 Diabetes (T2D), and several common cancers (Esposito et al., 2012; Hunt et al., 2004; Laing et al., 2003; Lakka, 2002; Palmer and Toth, 2019). The reported prevalence of MetS is as high as 31% in the global adult population (Noubiap et al., 2022); rendering it as a predominant driver of the worldwide crisis of poor cardiovascular health, cancer, and T2D (Dattani et al., 2019; World Health Organization, 2020). Regular exercise has a profound effect in improving the risk factors included in MetS (Dalleck et al., 2014; 2013; Roberts et al., 2013); therefore, weekly minimum amounts have been established, recommended, and disseminated globally (Liguori et al., 2021). Despite the plethora of evidence demonstrating the benefits of exercise, only 1 in 4 adults worldwide meet these recommendations (Whitfield et al., 2021; World Health Organization, 2022). The most common reported barriers to this are “lack of time,” “lack of facilities,” and “lack of motivation” (Costello et al., 2011; Justine et al., 2013). This information highlights the imperative to create strategies that overcome these barriers, and to investigate the efficacy of these strategies in reducing the global MetS burden.

Increasing in popularity is a form of exercise known as High-Intensity Functional Training (HIFT); that combines vigorous aerobic and resistance exercises into a time-efficient workout (Feito et al., 2018; Kercher et al., 2023). There are a range of design options for HIFT workouts, often requiring minimal equipment and allowing adaptability to various physical settings (Browne et al., 2020; Feito et al., 2018). HIFT has been shown to elicit positive psychological affect, and participation adherence, as well as high exercise enjoyment and strong intentions to continue (Heinrich et al., 2020; 2014). HIFT might therefore be a viable strategy for increasing exercise participation given its potential to alleviate known barriers.

The efficacy of HIFT at reducing MetS severity is emerging. In a study (Fealy et al., 2018) of 13 middle-aged adults clinically diagnosed with non-insulin dependent T2D, HIFT performed 3 times per week for 6 weeks improved diastolic blood pressure (DBP) (p < 0.01) and blood triglycerides (TG) (p < 0.05). Reductions (albeit insignificant) in waist circumference (WC) and systolic blood pressure (SBP) were also experienced (Fealy et al., 2018). The improvement in these risk factors resulted in a reduction in the MetS z-score (p = <0.001); an estimate of health risk based on the five MetS risk factors (Fealy et al., 2018; Gurka et al., 2014). In another study (Feito et al., 2019) of 18 overweight/obese adults, but metabolically healthier than the participants in the study by Fealy et al., (2018), 8-weeks of HIFT was compared to 8-weeks of the established exercise recommendations (Ligouri et al., 2021) to see if differences occurred in glucose control and WC. Even though baseline measures were not considered within the MetS range, WC improved, albeit insignificantly in both groups (Feito et al., 2019). To our knowledge, the majority of HIFT research has used healthy populations, therefore more scientific inquiry is needed to determine the effect on MetS in a symptomatic cohort.

The five risk factors used to diagnose MetS have developed over years of consultation among many organizations (Alberti et al., 2006; 1998; ATP III, 2002; Balkau and Charles, 1999). The aim was to establish simple criteria to confirm this syndrome in the clinical setting. Despite having established cut-offs for diagnosis, it is understood that a spectrum exists within these risk factors, and that another set of underlying risk factors (i.e. insulin resistance, atherogenic dyslipidemia, endothelial dysfunction, abnormal body fat distribution) give rise to these criteria (Grundy et al., 2005). It has been proposed that these additional underlying risk factors be included in investigations for the prevention and treatment of MetS (Alberti et al., 2006). Fealy et al., (2018) explored insulin resistance proxy markers by conducting an oral glucose tolerance test (OGTT) and calculating an insulin sensitivity score, and also body fat distribution via dual-energy x-ray absorptiometry (DEXA). The researchers found that insulin sensitivity improved in this population (p < 0.05), postulated as an overall downward shift in the glucose response to the OGTT (Fealy et al., 2018). They also saw regional reductions in body fat, notably android fat (p < 0.05), gynoid fat (p < 0.01), trunk fat (p < 0.05), and leg fat (p < 0.0001) (Fealy et al., 2018). In this same population, pancreatic β-cell function was measured as the mathematical product of insulin secretion and sensitivity, before and after a 6-week HIFT intervention (Nieuwoudt et al., 2017). Improvements were seen in these T2D adults (p < 0.05), representing more efficiency in the processing of insulin within the pancreatic β-cells (Nieuwoudt et al., 2017).

These studies indicate the potential positive effect HIFT may have on metabolic dysfunction, warranting further exploration into the previously mentioned underlying risk factors. Additionally, the participants in the above-mentioned studies exercised 3 times per week and therefore it is unknown if improvements could be seen with lower weekly frequency prescriptions. Minimal dose exercise research has been explored in other modalities, but not with HIFT (Batrakoulis et al., 2019; Grgic et al., 2018; Schoenfeld et al., 2019; Stavrinou et al., 2018). Establishing minimal doses offers more insight into solutions for the exercise barrier of “lack of time.” For these reasons, our aim was to investigate the weekly frequency dose-effects of HIFT on an array of blood lipids and lipoproteins, glucose, insulin and the homeostatic assessment of insulin resistance (HOMA-IR), metabolic syndrome severity, and body composition in adult men and women with MetS. Furthermore, we aimed to report their perceptions of exercise enjoyment and intention to continue after 12-weeks of different weekly doses of HIFT.

Twenty-seven participants were enrolled, 4 participants withdrew due to health complications unrelated to the study (HIFT1: N = 3; HIFT2: N = 1) and 2 dropped out due to unforeseen family and work interruptions (HIFT1: N = 1; HIFT2: N = 1). Twenty-one participants completed the full intervention (HIFT1: N = 4, HIFT2: N = 8, HIFT3: N = 9) with an adherence rate between 85-100%. Participant characteristics from the eligibility screening (Table 1) and all baseline outcome variables were similar between groups (p > 0.050). A Wilcoxon test revealed no differences in pre-to-post SLIQ for each group (p > 0.050) indicating participants maintained their current lifestyle behaviors throughout the intervention period.

Table 2-5 present the baseline (Pre) and 12-week follow-up (Post) data for each of the frequency dose groups, and includes the within group effect sizes and 95% confidence intervals. The preliminary two-way ANOVA and mixed-effects p-values are also included. Table 6 presents the one-way ANOVA results for the 12-week follow-up (Post) time point only.

The purpose of this investigation was to explore the effects of different weekly frequencies of a 50-55 min HIFT protocol for 12 weeks in order to elucidate a minimal weekly ‘frequency’ dose for meaningful improvements in MetS. The pooled time effect we observed for many health markers indicated positive change regardless of frequency, providing provisional insight that lower weekly frequency doses elicited positive responses. These time effects were seen for blood glucose, HOMA-IR, LDL-T, waist circumference, sagittal abdominal diameter, the number of MetS risk factors, and the MSSS. Time effects for improvements in VO₂ and workload at both VT1 and VT2 were also found. Additionally, HIFT increased the participants’ perception of cardiorespiratory fitness, muscular strength, speed & agility, and flexibility, regardless of dose group. In the exercise enjoyment survey, all three groups reported similar PACES scores, falling within the 80^th and 85^th percentile, and reported similarly on the “likeliness to continue” question within the 80^th and 89^th percentile. This indicates that regardless of the weekly frequency, relatively high enjoyment was experienced. Once again, all three groups reported within a similar range (3.0-3.3 days out of 7) on the “preferred dose per week” question.

A noteworthy finding, and of clinical relevance, is the reduction in MSSS we found in all three groups. The MSSS serves as a severity biomarker of metabolic derangement and addresses disease risk along a continuum rather than the defined risk factor cut-off points. The MSSS parallels the physiological continuum of development of metabolic dysfunction and therefore represents not only absolute disease risk but further residual risk beyond risk factor cut-off points (DeBoer et al., 2017; Golden et al., 2002; Gurka et al., 2017). In a study by DeBoer et al. (2018), the MSSS was used to track risk for future development of T2D and ASCVD for a 5-year period after a 1-year lifestyle or metformin intervention, in 2,476 adults with prediabetes. The researchers calculated 1-year change in MSSS effect sizes as well as hazard ratios for prediction of future disease for both interventions (DeBoer et al., 2018). They found a MSSS reduction effect size for the lifestyle intervention of 0.62 and effect size for metformin of 0.23. Upon risk prediction analysis, DeBoer et al. (2018) found that the degree of reduction in MSSS was associated with a proportional reduction in risk for future T2D and ASCVD (DeBoer et al., 2018). This demonstrates that a MSSS reduction effect size as little as 0.23 has health benefits and therefore is clinically meaningful. In our study, we found a MSSS reduction effect size of 0.28 for the HIFT1 group, which is similar to the metformin intervention mentioned previously. Our HIFT2 group saw the strongest effect size of 1.20, with HIFT3 only slightly lower at 1.07. If the degree of reduction in MSSS is proportionally associated with a reduction in risk for future disease, HIFT2 demonstrates the strongest clinical relevance for improving MetS severity. Not only is this clinically meaningful, but HIFT2 is practically meaningful as the time commitment is only 2 hours per week. Similarly, the individuals with T2D in the Fealy et al. (2018) study experienced a reduction in MSSS (-110%, p < 0.001). This was a larger percent reduction than our study, however this could be due to a greater baseline MSSS in the Fealy et al. (2018) participants thus permitting more room for improvement.

DeBoer et al. (2018) looked at the individual MetS risk factors and what proportion of the reduction in disease risk was attributable to each, noting that waist circumference and blood glucose changes provided a proportion of T2D risk prediction similar to that of changes in MSSS (75.0%, 48.2%, and 61.6%, respectively) (DeBoer et al., 2018). The magnitude of change in these risk factors proportionally reduced the risk for T2D (DeBoer et al., 2018). Their findings corroborate the clinical importance of the waist circumference and blood glucose changes we saw in our study. All dose groups demonstrated improvements in waist circumference (HIFT1: -4.1cm, HIFT2: -5.4cm, HIFT3: -0.7cm) and blood glucose (HIFT1: -9.5mg/dL, HIFT2: -4.9mg/dL, HIFT3: -1.7mg/dL), potentiating proportional risk reduction in T2D. Fealy et al. (2018) and Feito et al. (2019) noted reductions, albeit insignificant in waist circumference (-2.0 cm, p = 0.11 and -1.4 cm, p > 0.05, respectively) less than our HIFT1 and HIFT2 groups, but greater than our HIFT3 group. Additionally, Nieuwoudt et al. (2017) reported improvements in blood glucose (-4.9 mg.dL, p = 0.19) similar to our HIFT2 group, but less than our HIFT1 and greater than HIFT3. Comparable to the trend seen in MSSS, HIFT2 resulted in strong effects for these predictive markers.

To our knowledge, this is the first exploration using a population with MetS, distinct from T2D and overweight/obese, as well as the first exploration into a minimal effective weekly HIFT frequency. We postulate though, that the differences, in regards to waist circumference and blood glucose, between what we found and what was reported in Fealy et al. (2018), Nieuwoudt et al. (2017), and Feito et al. (2019), could perhaps indicate an influence of chronic dose, rather than simply weekly frequency. The participants in Fealy et al. (2018) and Nieuwoudt et al. (2017) completed 18 total HIFT sessions (3x/wk for 6 wks) and the participants in Feito et al. (2019) completed 24 total HIFT sessions (3x/wk for 8 wks). All three studies had a greater chronic dose than our HIFT1 group at 12 total sessions, were close to our HIFT2 group at 24 total sessions, but less than our HIFT3 group at 36 total sessions. All three studies along with our HIFT1 and HIFT2 groups had greater improvements in waist circumference and blood glucose than our HIFT3 group.

We speculate that the total volume dose for HIFT3 could have been more physiological stress than what was beneficial for this population. In a review of the inflammatory responses of HIFT, interleukin-6 (IL-6) was found to be acutely elevated after a training session, returning to basal levels at 48 hrs (Jacob et al., 2020), although in asymptomatic men and women with HIFT training experience. This acute inflammatory response though, is attributed to the hormetic effect leading to the desired exercise adaptations. Inflammatory markers, particularly IL-6 and C-reactive protein (CRP), can also be present in the body without the physiological stress of exercise, and represent a marker of systemic inflammation that predicts future atherosclerotic events (Ridker et al., 2000a; 2000b). This is often proposed as one of the reasons individuals with MetS have a greater risk for ASCVD, as CRP (Festa et al., 2000) and IL-6 (Van Guilder et al., 2006) chronically accompany MetS. Our participants, potentially in a chronic pro-inflammatory state, were subjected to progressive volumes of the acute inflammatory response of HIFT, with inversely reduced periods of recovery between sessions. Perhaps the coupled inflammatory stress of MetS and the HIFT exercise, reached a point of limited benefit in the HIFT3 group, who experienced the most volume and least recovery. Parallels of chronic IL-6 are seen in studies of excessive exercise training with reduced recovery in healthy populations, which disrupts the hormetic balance (Da Rocha et al., 2019). As a result, insulin signaling was impaired in multiple organs (Da Rocha et al., 2019) as well as impaired skeletal muscle glucose tolerance (Flockhart et al., 2021). Although we did not measure inflammatory markers in our participants, this could be a plausible reason for the diminishing benefits in glucose and waist circumference seen in our HIFT3 group, as both are known to be linked to insulin resistance.

With an additional barrier to exercise adherence being reported as “lack of motivation” (Costello et al., 2011; Justine et al., 2013), and knowing that higher ratings of enjoyment are linked to whether people are motivated to continue the exercise behavior (Kwan and Bryan, 2010), we wanted to know how our participants rated their enjoyment and intention to continue and if there were differences in the frequency groups. Our findings demonstrated that regardless of how many times per week the participants performed HIFT, their ratings of enjoyment and intention to continue were not different, and all groups rated above the 80^th percentile of possible scores; a higher score meaning higher enjoyment. Our findings conflict with Ekkekakis et al. (2011). These authors state that feelings of pleasure and enjoyment decrease after exercise intensity surpasses the first ventilatory threshold (Ekkekakis et al., 2011). However, our intervention required exercise well beyond this intensity, with VO₂ ranging between 88.8 ± 12.3% and 99.0 ± 12.0% of the second ventilatory threshold (Smith et al., 2022b), yet our participants still reported pleasure. Some high-intensity interval training (HIIT) intervention studies suggest that when exercising at higher intensities, the shorter the intervals (1 to 2 minutes) elicit greater enjoyment than longer intervals (20-40 minutes) (Jung et al., 2014; Martinez et al., 2015). Our intervention required intervals of 6 minutes, repeated 4 times (Smith et al., 2022a). Our findings are in line with Heinrich et al. (2014), where enjoyment and intention to continue was compared between a HIFT protocol and combined protocol following the ACSM published guidelines. The HIFT participants spent less time exercising than the other group, and reported greater enjoyment and intention to continue (Heinrich et al., 2014). Differing from the HIIT protocols in the previous studies, HIFT incorporates greater variety of movement with the resistance exercise component (Feito et al., 2018). It is suggested that the variety of exercises involved in HIFT may cause new participants to focus on mastery-based goals (Partridge et al., 2014), which has shown to foster intrinsic interest in the activity (Elliot and McGregor, 2001). Our intervention was delivered in a group setting which allowed for connection between the participants. In a similar HIFT group intervention evaluating the participants “sense of community,” the authors found this perception to be highly rated and that it influenced their enjoyment of the study (Heinrich et al., 2022). Although we did not measure this affective response, perhaps our similar setting created this group dynamic that led to our higher ratings of enjoyment.

A strength to our study was the application of mesocycle periodization. Within a 4-week block, training load was strategically applied for 3 of the weeks followed by 1 week of reduced load, prior to a progression of load into the next 4-week block. This strategy provides adequate stimulation for training adaptation along with a recovery period to ensure physiological absorption of the adaptations and management of fatigue (Plisk and Stone, 2003). Given the intense nature of HIFT and the efficacy of this strategy shown by endurance and strength coaches (Turner, 2011), periodization was deemed appropriate for our population and duration of training. Our intention to conduct this intervention in a translatable, non-laboratory, real-world setting, was another strength. The modality of HIFT has the ability to be performed in group or solo situations, as well as in home, gym, work, outdoor, and travel physical settings requiring minimal equipment (Feito et al., 2018). This translatability proposes a solution to the “lack of facilities” barrier to exercise. But this real-world approach led to a limitation in our study, as the data collection period was within the COVID-19 pandemic. During this time several community infection surges occurred, masking and group size regulations were a moving boundary, and quarantine regulations were required with a positive COVID test. The delays, restrictions, and community concerns hindered our recruitment, contributing to our small sample size, leading to the study being underpowered (Corsello et al., 2020). Additionally, it is unknown how much affect the residual health complications from COVID infections had on our participant’s outcomes, but it had known effect on adherence. Throughout the study period, several of our participants tested positive for COVID, were symptomatic and required quarantine. Two participants had such severe infections they were unable to continue. This once again contributed to our small sample size. We encourage future studies to replicate and progress our research questions, as HIFT shows promise toward effectiveness and exercise adherence. To facilitate this, our full methodology is published (Smith et al., 2022a).

In summary, HIFT performed once, twice, or thrice weekly for 12 weeks similarly improved a range of cardiometabolic health markers in participants with MetS, and was regarded as an enjoyable modality of exercise.